Although the chemical identity of leukotrienes was not discovered until 1979, their history actually began in Australia in 1938 when researchers discovered slow reacting substances (SRS) which caused slow contractions of smooth muscle. When their chemical identity was learned, SRS was found to be a mixture of three previously unknown substances which are related chemically to the prostaglandins and thromboxanes. They were named leukotrienes because they are made by leukocytes and have three conjugated double bonds. Leukotrienes have major effects on the smaller peripheral airways of the lungs and on the larger central passages which include the trachea and the bronchi. In the presence of an allergy trigger, like pollen or dust, leukotrienes are manufactured from fatty substances trapped in the membrane of a triggered cell. A series of reactions within the cell generates a set of different leukotrienes which are transported through the cell membrane into the blood. Then they bring about a constriction of the air passages leading to breachlessness. In addition, the leukotrienes have been implicated as mediators of numerous other disease states, including inflammation, skin diseases and allergic reactions, among others. See, for example; D. M. Bailey et al., Ann. Rpts. Med. Chem. 17 203 (1982).
Several classes of compounds are known to be leukotriene antagonists. See for example: Great Britain Patent Specification No. 2,058,785 disclosing phenoxyalkoxyphenyl compounds which are useful as antagonists of the slow reacting substance of anaphylaxis; European patent application No. 56,172 disclosing phenoxy and thiophenoxy compounds which are useful as antagonists of the slow reacting substance of anaphylaxis; European patent application No. 61,800 disclosing anti-SRS-A bicyclic carboxylic acid derivatives.